Chancroid, an ulcerogenital disease caused by the fastidious gram-negative bacterium Haemophilus ducreyi, is one of the least understood sexually transmitted diseases. The incidence of this disease has increased dramatically in this country over the last five years, and the reported association between genital ulcer disease and transmission of the human immunodeficiency virus makes control and prevention of this disease a public health concern. This research project involves a comprehensive approach to the study of chancroid. 1) A newly developed, temperature-dependent rabbit model for lesion production by H. ducreyi will be used to investigate the pathogenesis of this disease. This model system will permit experimental investigation of basic issues related to the host-parasite interaction in chancroid. 2) Mutant analysis will be used to identify virulence factors of this pathogen. Both monoclonal antibody techniques and recombinant DNA methods will be used in conjunction with the newly developed animal model to elucidate the virulence mechanisms involved in the production of skin lesions by H. ducreyi. 3) The practical difficulties associated with making a specific diagnosis of chancroid will be addressed through the identification of diagnostic probes for this pathogen. Both monoclonal antibody- and nucleic acid-based probes will be investigated for their abilities to detect this pathogen in clinically relevant samples. Integration of studies on the pathogenesis of chancroid with efforts to develop diagnostic probes for H. ducreyi will enhance our efforts and abilities in both areas.